Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 Clinical Trial.

IMPORTANCE: Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. OBJECTIVES: To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. DESIGN, SETTING, AND PARTICIPANTS: The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. INTERVENTIONS: Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. MAIN OUTCOMES AND MEASURES: The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis-free survival, overall survival, and circulating tumor cell incidence. RESULTS: A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) for ERBB2 (formerly HER2 or HER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis-free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. CONCLUSIONS AND RELEVANCE: For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PURPOSE: To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. METHODS AND MATERIALS: Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). RESULTS: Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue. CONCLUSION: Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare.

A novel two-step optimization method for tandem and ovoid high-dose-rate brachytherapy treatment for locally advanced cervical cancer.

PURPOSE: To present a novel method allowing fast volumetric optimization of tandem and ovoid high-dose-rate treatments and to quantify its benefits. METHODS AND MATERIALS: Twenty-seven CT-based treatment plans from 6 consecutive cervical cancer patients treated with four to five intracavitary tandem and ovoid insertions were used. Initial single-step optimized plans were manually optimized, approved, and delivered plans created with a goal to cover high-risk clinical target volume (HR-CTV) with D90 >90% and minimize rectum, bladder, and sigmoid D2cc. For the two-step optimized (TSO) plan, each single-step optimized plan was replanned adding a structure created from prescription isodose line to the existent physician delineated HR-CTV, rectum, bladder, and sigmoid. New, more rigorous dose-volume histogram constraints for the critical organs at risks (OARs) were used for the optimization. HR-CTV D90 and OAR D2ccs were evaluated in both plans. RESULTS: TSO plans had consistently smaller D2ccs for all three OARs while preserving HR-CTV D90. On plans with "excellent" CTV coverage, average D90 of 96% (91-102%), sigmoid, bladder, and rectum D2cc, respectively, reduced on average by 37% (16-73%), 28% (20-47%), and 27% (15-45%). Similar reductions were obtained on plans with "good" coverage, average D90 of 93% (90-99%). For plans with "inferior" coverage, average D90 of 81%, the coverage increased to 87% with concurrent D2cc reductions of 31%, 18%, and 11% for sigmoid, bladder, and rectum, respectively. CONCLUSIONS: The TSO can be added with minimal planning time increase but with the potential of dramatic and systematic reductions in OAR D2ccs and in some cases with concurrent increase in target dose coverage. These single-fraction modifications would be magnified over the course of four to five intracavitary insertions and may have real clinical implications in terms of decreasing both acute and late toxicities.

Examining the relationship between pre- and postimplant geometry in prostate low-dose-rate brachytherapy and its correlation with dosimetric quality using the similarity concept.

PURPOSE: This is a retrospective study in which we define multiple metrics for similarity and then inquire on the relationship between similarity and currently used dosimetric quantities describing preimplant and postimplant plans. METHODS AND MATERIALS: We analyzed a unique cohort of 94 consecutively performed prostate seed implant patients, associated with excellent dosimetric and clinical outcomes. For each patient, an ultrasound (US) preimplant and two CT postimplant (Day 0 and Day 30) studies were available. Measures for similarity were created and computed using feature vectors based on two classes of moments: first, invariant to rotation and translation, and the second polar-radius moments invariant to rotation, translation, and scaling. Both similarity measures were calibrated using controlled perturbations (random and systematic) of seed positions and contours in different size implants, thus producing meaningful numerical threshold values used in the clinical analysis. RESULTS: An important finding is that similarity, for both seed distributions and contours, improves significantly when scaling invariance is added to translation and rotation. No correlation between seed and contours similarity was found. In the setting of preplanned prostate seed implants using preloaded needles, based on our data, similarity between preimplant and postimplant plans does not correlate with either minimum dose to 90% of the volume of the prostate or analogous similarity metrics for prostate contours. CONCLUSIONS: We have developed novel tools and metrics, which will allow practitioners to better understand the relationship between preimplant and postimplant plans. Geometrical similarity between a preplan and an actual implant, although useful, does not seem to be necessary to achieve minimum dose to 90% of the volume of the prostate-good dosimetric implants.

Contura Multi-Lumen Balloon breast brachytherapy catheter: comparative dosimetric findings of a phase 4 trial.

PURPOSE: Final dosimetric findings of a completed, multi-institutional phase 4 registry trial using the Contura Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer are presented. METHODS AND MATERIALS: Three dosimetric plans with identical target coverage were generated for each patient for comparison: multilumen multidwell (MLMD); central-lumen multidwell (CLMD); and central-lumen single-dwell (CLSD) loading of the Contura catheter. For this study, a successful treatment plan achieved ideal dosimetric goals and included the following: ≥ 95% of the prescribed dose (PD) covering ≥ 95% of the target volume (TV); maximum skin dose ≤ 125% of the PD; maximum rib dose ≤ 145% of the PD; and V150 ≤50 cc and V200 ≤ 10 cc. RESULTS: Between January 2008 and February 2011, 23 institutions participated. A total of 318 patients were available for dosimetric review. Using the Contura MLB, all dosimetric criteria were met in 78.93% of cases planned with MLMD versus 55.38% with the CLMD versus 37.66% with the CLSD (P ≤.0001). Evaluating all patients with the full range of skin to balloon distance represented, median maximum skin dose was reduced by 12% and median maximum rib dose by 13.9% when using MLMD-based dosimetric plans compared to CLSD. The dosimetric benefit of MLMD was further demonstrated in the subgroup of patients where skin thickness was <5 mm, where MLMD use allowed a 38% reduction in median maximum skin dose over CLSD. For patients with rib distance <5 mm, the median maximum rib dose reduction was 27%. CONCLUSIONS: Use of the Contura MLB catheter produced statistically significant improvements in dosimetric capabilities between CLSD and CLMD treatments. This device approach demonstrates the ability not only to overcome the barriers of limited skin thickness and close rib proximity, but to consistently achieve a higher standard of dosimetric planning goals.

Ultrashort courses of adjuvant breast radiotherapy: wave of the future or a fool's errand?

In accelerated partial breast irradiation (APBI), the most commonly used fractionation schemes include 340 or 385 centigrays delivered in a twice daily administration. A further progression of the APBI literature has been the recent interest in extremely short courses of adjuvant radiotherapy, usually delivered by intraoperative radiotherapy techniques. This newer area of single-fraction radiotherapy approaches remains highly contentious. In particular, the recently reported TARGIT trial has been the subject of both praise and scorn, and a critical examination of the trial data and the underlying hypotheses is warranted. Short-term outcomes of the related Italian ELIOT approach have also been reported. Although the assumptions of linear quadratic formalism are likely to hold true in the range of 2 to 8 grays, equating different schedules beyond this range is problematic. A major problem of current single-fraction approaches is that the treatment doses are chosen empirically, or are based on tolerability, or on the physical dose delivery characteristics of the chosen technology rather than radiobiological rationale. This review article summarizes the current data on ultrashort courses of adjuvant breast radiotherapy and highlights both the promise and the potential pitfalls of the abbreviated treatment.

A novel method for accurate needle-tip identification in trans-rectal ultrasound-based high-dose-rate prostate brachytherapy.

PURPOSE: In real-time trans-rectal ultrasound (TRUS)-based high-dose-rate prostate brachytherapy, the accurate identification of needle-tip position is critical for treatment planning and delivery. Currently, needle-tip identification on ultrasound images can be subject to large uncertainty and errors because of ultrasound image quality and imaging artifacts. To address this problem, we developed a method based on physical measurements with simple and practical implementation to improve the accuracy and robustness of needle-tip identification. METHODS AND MATERIALS: Our method uses measurements of the residual needle length and an off-line pre-established coordinate transformation factor, to calculate the needle-tip position on the TRUS images. The transformation factor was established through a one-time systematic set of measurements of the probe and template holder positions, applicable to all patients. To compare the accuracy and robustness of the proposed method and the conventional method (ultrasound detection), based on the gold-standard X-ray fluoroscopy, extensive measurements were conducted in water and gel phantoms. RESULTS: In water phantom, our method showed an average tip-detection accuracy of 0.7 mm compared with 1.6 mm of the conventional method. In gel phantom (more realistic and tissue-like), our method maintained its level of accuracy while the uncertainty of the conventional method was 3.4mm on average with maximum values of over 10mm because of imaging artifacts. CONCLUSIONS: A novel method based on simple physical measurements was developed to accurately detect the needle-tip position for TRUS-based high-dose-rate prostate brachytherapy. The method demonstrated much improved accuracy and robustness over the conventional method.

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PURPOSE: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. METHODS AND MATERIALS: Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. RESULTS: The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. CONCLUSIONS: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.

Localizing intracavitary brachytherapy applicators from cone-beam CT x-ray projections via a novel iterative forward projection matching algorithm.

PURPOSE: To present a novel method for reconstructing the 3D pose (position and orientation) of radio-opaque applicators of known but arbitrary shape from a small set of 2D x-ray projections in support of intraoperative brachytherapy planning. METHODS: The generalized iterative forward projection matching (gIFPM) algorithm finds the six degree-of-freedom pose of an arbitrary rigid object by minimizing the sum-of-squared-intensity differences (SSQD) between the computed and experimentally acquired autosegmented projection of the objects. Starting with an initial estimate of the object's pose, gIFPM iteratively refines the pose parameters (3D position and three Euler angles) until the SSQD converges. The object, here specialized to a Fletcher-Weeks intracavitary brachytherapy (ICB) applicator, is represented by a fine mesh of discrete points derived from complex combinatorial geometric models of the actual applicators. Three pairs of computed and measured projection images with known imaging geometry are used. Projection images of an intrauterine tandem and colpostats were acquired from an ACUITY cone-beam CT digital simulator. An image postprocessing step was performed to create blurred binary applicators only images. To quantify gIFPM accuracy, the reconstructed 3D pose of the applicator model was forward projected and overlaid with the measured images and empirically calculated the nearest-neighbor applicator positional difference for each image pair. RESULTS: In the numerical simulations, the tandem and colpostats positions (x,y,z) and orientations (alpha, beta, gamma) were estimated with accuracies of 0.6 mm and 2 degrees, respectively. For experimentally acquired images of actual applicators, the residual 2D registration error was less than 1.8 mm for each image pair, corresponding to about 1 mm positioning accuracy at isocenter, with a total computation time of less than 1.5 min on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, fast, and completely automatic method to localize radio-opaque applicators of arbitrary shape from measured 2D x-ray projections. The results demonstrate approximately 1 mm accuracy while compared against the measured applicator projections. No lateral film is needed. By localizing the applicator internal structure as well as radioactive sources, the effect of intra-applicator and interapplicator attenuation can be included in the resultant dose calculations. Further validation tests using clinically acquired tandem and colpostats images will be performed for the accurate and robust applicator/sources localization in ICB patients.

Reconstruction of brachytherapy seed positions and orientations from cone-beam CT x-ray projections via a novel iterative forward projection matching method.

PURPOSE: To generalize and experimentally validate a novel algorithm for reconstructing the 3D pose (position and orientation) of implanted brachytherapy seeds from a set of a few measured 2D cone-beam CT (CBCT) x-ray projections. METHODS: The iterative forward projection matching (IFPM) algorithm was generalized to reconstruct the 3D pose, as well as the centroid, of brachytherapy seeds from three to ten measured 2D projections. The gIFPM algorithm finds the set of seed poses that minimizes the sum-of-squared-difference of the pixel-by-pixel intensities between computed and measured autosegmented radiographic projections of the implant. Numerical simulations of clinically realistic brachytherapy seed configurations were performed to demonstrate the proof of principle. An in-house machined brachytherapy phantom, which supports precise specification of seed position and orientation at known values for simulated implant geometries, was used to experimentally validate this algorithm. The phantom was scanned on an ACUITY CBCT digital simulator over a full 660 sinogram projections. Three to ten x-ray images were selected from the full set of CBCT sinogram projections and postprocessed to create binary seed-only images. RESULTS: In the numerical simulations, seed reconstruction position and orientation errors were approximately 0.6 mm and 5 degrees, respectively. The physical phantom measurements demonstrated an absolute positional accuracy of (0.78 +/- 0.57) mm or less. The theta and phi angle errors were found to be (5.7 +/- 4.9) degrees and (6.0 +/- 4.1) degrees, respectively, or less when using three projections; with six projections, results were slightly better. The mean registration error was better than 1 mm/6 degrees compared to the measured seed projections. Each test trial converged in 10-20 iterations with computation time of 12-18 min/iteration on a 1 GHz processor. CONCLUSIONS: This work describes a novel, accurate, and completely automatic method for reconstructing seed orientations, as well as centroids, from a small number of radiographic projections, in support of intraoperative planning and adaptive replanning. Unlike standard back-projection methods, gIFPM avoids the need to match corresponding seed images on the projections. This algorithm also successfully reconstructs overlapping clustered and highly migrated seeds in the implant. The accuracy of better than 1 mm and 6 degrees demonstrates that gIFPM has the potential to support 2D Task Group 43 calculations in clinical practice.

Optimal application of the Contura multilumen balloon breast brachytherapy catheter vacuum port to deliver accelerated partial breast irradiation.

PURPOSE: The impact of using the Contura multilumen balloon (MLB) (SenoRx, Inc., Irvine, CA) breast brachytherapy catheter's vacuum port in patients treated with accelerated partial breast irradiation (APBI) was analyzed. METHODS AND MATERIALS: Data from 32 patients at two sites were reviewed. Variables analyzed included the seroma fluid (SF):air volume around the MLB before and after vacuum port use and on its ability to improve (1) the eligibility of patients for APBI and (2) dose coverage of the planning target volume for evaluation (PTV_EVAL) in eligible patients. RESULTS: The median SF/air volume before vacuum removal was 6.8 cc vs. 0.8 cc after vacuum removal (median reduction in SF/air volume was 90.5%). Before vacuum port use, the median SF/air volume expressed as percentage of the PTV_EVAL was 7.8% (range, 1.9-26.6) in all patients. After application of the vacuum, this was reduced to 1.2%. Before vacuum port use, 10 (31.3%) patients were not considered acceptable candidates for APBI because the SF/air volume:PTV_EVAL ratio (SF:PTV) was greater than 10% (range, 10.1-26.6%; median, 15.2%). After vacuum port use, the median SF:PTV ratio was 1.6% for a median reduction of 91.5%. In addition, the percentage of the prescribed dose covering greater than or equal to 90% of the PTV_EVAL proportionally increased a median of 8% (range, 3-10%) in eligible patients. CONCLUSION: Use of the Contura MLB vacuum port significantly improved the conformity of the target tissue to the balloon surface, leading to reproducible dose delivery and increased target volume coverage. In addition, application of the vacuum allowed the safe treatment of unacceptable patients with APBI.

Improvements in critical dosimetric endpoints using the Contura multilumen balloon breast brachytherapy catheter to deliver accelerated partial breast irradiation: preliminary dosimetric findings of a phase iv trial.

PURPOSE: Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented. METHODS AND MATERIALS: Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) ≥95% of the prescribed dose (PD) covering ≥90% of the target volume, (2) a maximum skin dose ≤125% of the PD, (3) maximum rib dose ≤145% of the PD, and (4) the V150 ≤50 cc and V200 ≤10 cc. The ability to concurrently achieve these dosimetric goals using the Contura MLB was analyzed. RESULTS: 144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was ≥5 mm to <7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was <5 mm, the median skin dose was 124.2%. When rib distance was <5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was <7 mm and distance to rib was <5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively. CONCLUSION: The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered.

Clinical application and validation of an iterative forward projection matching algorithm for permanent brachytherapy seed localization from conebeam-CT x-ray projections.

PURPOSE: To experimentally validate a new algorithm for reconstructing the 3D positions of implanted brachytherapy seeds from postoperatively acquired 2D conebeam-CT (CBCT) projection images. METHODS: The iterative forward projection matching (IFPM) algorithm finds the 3D seed geometry that minimizes the sum of the squared intensity differences between computed projections of an initial estimate of the seed configuration and radiographic projections of the implant. In-house machined phantoms, containing arrays of 12 and 72 seeds, respectively, are used to validate this method. Also, four 103Pd postimplant patients are scanned using an ACUITY digital simulator. Three to ten x-ray images are selected from the CBCT projection set and processed to create binary seed-only images. To quantify IFPM accuracy, the reconstructed seed positions are forward projected and overlaid on the measured seed images to find the nearest-neighbor distance between measured and computed seed positions for each image pair. Also, the estimated 3D seed coordinates are compared to known seed positions in the phantom and clinically obtained VariSeed planning coordinates for the patient data. RESULTS: For the phantom study, seed localization error is (0.58 +/- 0.33) mm. For all four patient cases, the mean registration error is better than 1 mm while compared against the measured seed projections. IFPM converges in 20-28 iterations, with a computation time of about 1.9-2.8 min/ iteration on a 1 GHz processor. CONCLUSIONS: The IFPM algorithm avoids the need to match corresponding seeds in each projection as required by standard back-projection methods. The authors' results demonstrate approximately 1 mm accuracy in reconstructing the 3D positions of brachytherapy seeds from the measured 2D projections. This algorithm also successfully localizes overlapping clustered and highly migrated seeds in the implant.

Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO).

PURPOSE: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. RESULTS: The Task Force proposed three patient groups: (1) a "suitable" group, for whom APBI outside of a clinical trial is acceptable, (2) a "cautionary" group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an "unsuitable" group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. CONCLUSION: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

Demonstration of a forward iterative method to reconstruct brachytherapy seed configurations from x-ray projections.

By monitoring brachytherapy seed placement and determining the actual configuration of the seeds in vivo, one can optimize the treatment plan during the process of implantation. Two or more radiographic images from different viewpoints can in principle allow one to reconstruct the configuration of implanted seeds uniquely. However, the reconstruction problem is complicated by several factors: (1) the seeds can overlap and cluster in the images; (2) the images can have distortion that varies with viewpoint when a C-arm fluoroscope is used; (3) there can be uncertainty in the imaging viewpoints; (4) the angular separation of the imaging viewpoints can be small owing to physical space constraints; (5) there can be inconsistency in the number of seeds detected in the images; and (6) the patient can move while being imaged. We propose and conceptually demonstrate a novel reconstruction method that handles all of these complications and uncertainties in a unified process. The method represents the three-dimensional seed and camera configurations as parametrized models that are adjusted iteratively to conform to the observed radiographic images. The morphed model seed configuration that best reproduces the appearance of the seeds in the radiographs is the best estimate of the actual seed configuration. All of the information needed to establish both the seed configuration and the camera model is derived from the seed images without resort to external calibration fixtures. Furthermore, by comparing overall image content rather than individual seed coordinates, the process avoids the need to establish correspondence between seed identities in the several images. The method has been shown to work robustly in simulation tests that simultaneously allow for unknown individual seed positions, uncertainties in the imaging viewpoints and variable image distortion.